Homeopathy for COVID-19 in primary care: A randomized, double-blind, placebo-controlled trial (COVID-Simile study)

Background: Different homeopathic approaches have been used as supportive care for coronavirus disease 2019 (COVID-19) cases, but none has been tested in a clinical trial. Objectives: To investigate the effectiveness and safety of the homeopathic medicine, Natrum muriaticum LM2, for mild cases of COVID-19. Design, setting, participants, and interventions: A randomized, double-blind, two-armed, parallel, singlecenter, placebo-controlled clinical trial was conducted from June 2020 to April 2021 in Sao-Carlos, Brazil. Participants aged > 18 years, with influenza-like symptoms and positive result from a real-time polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 were recruited and randomized (1:1) into two groups that received different treatments during a period of at-homeisolation. One group received the homeopathic medicine Natrum muriaticum, prepared with the second degree of the fifty-millesimal dynamization (LM2; Natrum muriaticum LM2), while the other group received a placebo. Outcome measures: The primary endpoint was time until recovery from COVID-19 influenza-like symptoms. Secondary measures included a survival analysis of the number and severity of COVID-19 symptoms (influenza-like symptoms plus anosmia and ageusia) from a symptom grading scale that was informed by the participant, hospital admissions, and adverse events. Kaplan-Meier curves were used to estimate time-to-event (survival) measures. Results: Data from 86 participants were analyzed (homeopathy, n = 42; placebo, n = 44). There was no difference in time to recovery between two groups among participants who were reporting influenzalike symptoms at the beginning of monitoring (homeopathy, n = 41; placebo, n = 41; P = 0.56), nor in a sub-group that had at least 5 moderate to severe influenza-like symptoms at the beginning of monitoring (homeopathy, n = 15; placebo, n = 17; P = 0.06). Secondary outcomes indicated that a 50% reduction in symptom score was achieved significantly earlier in the homeopathy group (homeopathy, n = 24; placebo, n = 25; P = 0.04), among the participants with a basal symptom score >= 5. Moreover, values of restricted mean survival time indicated that patients receiving homeopathy might have improved 0.9 days faster during the first five days of follow-up (P = 0.022). Hospitalization rates were 2.4% in the homeopathy group and 6.8% in the placebo group (P = 0.62). Participants reported 3 adverse events in the homeopathy group and 6 in the placebo group. Conclusion: Results showed that Natrum muriaticum LM2 was safe to use for COVID-19, but there was no statistically significant difference in the primary endpoints of Natrum muriaticum LM2 and placebo for mild COVID-19 cases. Although some secondary measures do not support the null hypothesis, the wide confidence intervals suggest that further studies with larger sample sizes and more symptomatic participants are needed to test the effectiveness of homeopathic Natrum muriaticum LM2 for COVID-19. Trial registration: UMIN Clinical Trials Registry ID: JPRN-UMIN000040602. Please cite this article as: Adler UC, Adler MS, Padula AEM, Hotta LM, de Toledo Cesar A, Diniz JNM, de Freitas Santos H, Martinez EZ. Homeopathy for COVID-19 in primary care: A randomized, double-blind, placebo-controlled trial (COVID-Simile study). J Integr Med. 2022; 20(3): 221-229. (c) 2022 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier B.V. All rights reserved.